We propose to study genetic regulation of endogenous murine retroviruses, in relation to spontaneous murine leukemogenesis and as a general problem of spontaneous mammalian gene control. Our experimental plan will emphasize the murine genetic locus Fv-1. The primary goal is to further characterize cells derived from dually-sensitive SC-1 cells which spontaneously developed dual resistance to N- and B-tropic, but not to NB-tropic, viruses. Resistant cells and their antecedent sensitive cells will be cloned for further analysis. As these changes suggest possible alterations in cellular resistance to endogenous oncogenic viruses with aging and cellular differentiation, this suggest ion will be pursued in studies of different types of murine cells. Possible additional Fv-1 alleles, or additional cellular mechanisms, in the DBA/2 and NZB strains will be analysed. We hope to develop methods to study in tissue culture infection of lymphoid cells by endogenous retroviruses. We also hope to further characterize an RNA species reported to transfer Fv-1 resistance unto sensitive cells.